Project Summary The overarching goal of the project is to elucidate the mechanisms underlying the vestibular deficits due to exposure to blast overpressure waves, such as that produced by explosive devices. The project addresses an urgent need of the societies as nearly half of the service members who have experienced blast exposure showed vestibular signs and symptoms, e.g. dizziness, imbalance and vertigo, which increase fall risk and result in impaired performance during deployment and daily living. Lack of an understanding on the underlying mechanisms represents a critical knowledge gap in developing effective prevention, diagnosis and treatment programs of blast overpressure-induced vestibular deficits. The aim of the proposal is to fill the knowledge gap by developing a rodent model of blast- induced vestibular injuries and identifying the biomarkers of the underlying injuries. Different from current blast animal models in which blast overpressure waves are delivered over the whole head or the whole animal, a unique feature of our model is that we deliver precisely controlled blast overpressure waves (0~100psi) primarily into the external ear canal, therefore, avoiding impacting other air-filled organs. The present application will take advantage of the animal model to longitudinally assess acute-through-chronic anatomical, physiological and behavioral biomarkers of the vestibular deficits caused by blast exposure. Aim 1a is to examine the effects of blast exposure on vestibular hair cell morphology and Aim 1b is to study responses of vestibular afferents to head rotation and translation in rats. Aim 1c is to examine the effects of blast exposure on the central vestibular system, including brain stem vestibular nuclei and cerebellum. Expression of biomarkers for inflammation, neuronal/axonal damage, and blood-brain-barrier (BBB) disruptions will be examined. Aim 1d is to examine the effects of blast exposure on the vestibular ocular reflex (VOR) using sinusoidal and transient head rotation/translation. These aims will lay the foundation for understanding blast-induced peripheral and central vestibular injuries and contribute to addressing the clinical vestibular signs and symptoms after blast exposure.